This investigation is directed towards continuation of a study of the molecular pathology of the common inherited disorder of metabolism, cystic fibrosis of the pancreas (CF). Disturbances of secretion and cell transport appear to underlie much of the pathologic process in CF and there is convincing evidence that cultured cells from patients also manifest the presence of the CF gene. This has stimulated our development and application of methods for the analysis of the plasma membranes of CF fibroblasts. Presently we are evaluating the turnover of the proteins of this organelle. Other metabolic aspects of these cells, including the degradation of polyamines, are also under study. Recently, using preparations of isolated mitochondria, we have engaged in a collaborative effort to perfect a reliable quantitative assay for the membrane active "CF factors" found in patient secretions and produced by their cells in culture. This method will facilitate our attempts to purify and characterize chemically these substances which is essential for the understanding of their metabolic origin and pathogenetic significance. In addition the procedure has shown promise as an adjunct in the biochemical characterization of the CF phenotype - so variable at the clinical level. An understanding of this has important experimental and therapeutic implications.